Journal Of Pharmaceutical And Biomedical Analysis[JOURNAL]
Sun
200 papers
Strategic characterization of active pharmaceutical ingredients co-eluting impurities: Identification, enrichment and structural elucidation of an oxidized impurity from mobocertinib drug substance.
Dai Y, Li H, Guo R … +10 more , Zhu G, Grange RL, Yaji K, Takagi I, Moriguchi K, Milton MJ, Hu Y, Ma L, Santos WL, Zell MT
J Pharm Biomed Anal · 2026 Sep · PMID 41946236 · Publisher ↗
Mobocertinib (TAK-788) is a potent, synthetic molecule tyrosine kinase inhibitor specifically designed to selectively target epidermal growth factor receptor and HER2 exon 20 insertion mutations. Previously, it was a dru...
Mobocertinib (TAK-788) is a potent, synthetic molecule tyrosine kinase inhibitor specifically designed to selectively target epidermal growth factor receptor and HER2 exon 20 insertion mutations. Previously, it was a drug candidate developed by Takeda Pharmaceuticals used to treat patients with metastatic non-small cell lung cancer. During process development, a new oxidative degradant was identified as a co-eluting peak with the active pharmaceutical ingredient (API) in the release method. To understand the significance of this unknown co-eluting impurity, full structural characterization was performed by following a newly established workflow. In brief, preliminary two-dimensional LC-MS (2D-LC-MS) analysis identified the targeted degradant as a mono-oxygenated product of TAK-788. With the purpose of facile isolation and purification, various forced degradation conditions were screened to enrich the desired degradant, among which hydrogen peroxide-treatment effectively afforded a yield of 65% for this unknown impurity. Following isolation by prep-HPLC, 1D and 2D NMR studies and HRMS characterization assigned the isolate as Mobocertinib-N-oxide. In addition, NMR-based reaction monitoring was conducted to trace its formation, allowing a plausible mechanism of formation to be proposed.
Rapid, precise and multi-excipient benchtop H NMR method to monitor drug substance and drug product process consistency.
Esposito K, Sutton AT, Rustandi RR … +1 more , Schombs M
J Pharm Biomed Anal · 2026 Aug · PMID 41933981 · Publisher ↗
Vaccine and biologic manufacturing processes and formulations include a series of purification, filtration, and buffer exchanges. The complexity associated with these processes is increased with drug product images or mu...
Vaccine and biologic manufacturing processes and formulations include a series of purification, filtration, and buffer exchanges. The complexity associated with these processes is increased with drug product images or multiple component drug substance/drug products. Excipients from therapeutic protein media, buffers, and formulations each serve critical roles in stabilization, cryoprotection, and osmolality. Herein, we describe a simple and rapid quantitative H NMR method using a benchtop 90 MHz instrument for simultaneous measurement of excipients in aqueous formulations without the need for complex sample preparation or purification steps. The method employs minimal sample preparation and uses internal standards for accurate quantitation, which lends itself to Process Analytical Technology (PAT), with at-line measurements or in-process control testing. Despite the lower spectral resolution of a 90 MHz system compared to a high-resolution NMR, characteristic proton resonances were successfully resolved and quantitated, enabling reliable concentration determination of sucrose, propylene glycol (PG), and leucine and in the presence of therapeutic products. Spiked recoveries averaged 100.4% for sucrose, 101.1% for PG, and 100.5% for leucine with precision results less than 5% relative standard deviation, tested in the range of 4.5-27% w/v for sucrose, 0.25-1.5% w/v for PG, and 12.5-75 mM for leucine. This approach offers a cost-effective alternative for routine excipient analysis, with the added advantage that it is a non-destructive technique. The concentration of excipients determined by NMR can be correlated directly with osmolality and is particularly valuable for assessing formulation stability in complex matrices such as vaccines, biologics, and therapeutic proteins.
Environmental sustainability assessment of reverse-phase liquid chromatography for retention and ionization profiling of angiotensin-converting enzyme inhibitors.
Kuzucanlı E, Demiralay EÇ, Daldal YD … +1 more , Yilmaz H
J Pharm Biomed Anal · 2026 Aug · PMID 41932063 · Publisher ↗
This paper presents a sustainable chromatographic framework using reverse-phase liquid chromatography (RPLC) method with an ultraviolet detector (UV) to determine the ionization behavior of three angiotensin-converting e...
This paper presents a sustainable chromatographic framework using reverse-phase liquid chromatography (RPLC) method with an ultraviolet detector (UV) to determine the ionization behavior of three angiotensin-converting enzyme (ACE) inhibitors, benazepril, cilazapril, and quinapril, in a water-organic solvent binary mixture. In this study, retention-mobile phase pH data under various hydroorganic conditions were analyzed using nonlinear regression (NLREG) and linear solvation energy relationship (LSER) approaches to calculate the dissociation constant (pKass) values of the compounds. Accurate aqueous pK (pKaww) values are essential for predicting ionization-dependent solubility, chromatographic behavior, and biopharmaceutical performance of ACE inhibitors. Chromatographic experiments were conducted at 25 °C and 37 °C on a YMC Triart C18 column in ethanol-water, methanol-water, and acetonitrile-water mixtures (40-55% v/v). The pKaww values of the compounds in aqueous medium were calculated using two different temperatures and approaches. At 37 °C, pKa1ww values for cilazapril, benazepril, and quinapril were calculated as 3.715, 3.819, and 3.967, respectively; and pKa2ww values were calculated as 5.316, 5.187, and 5.226, respectively. The values calculated from these studies are compatible with each other and with the literature values. The dependence of the developed methods on twelve green analytical chemistry (GAC) principles was evaluated using the Analytical Greenness Metric (AGREE score=0.77), the Green Analytical Procedure Index (GAPI), and the Analytical Green Star Area (AGSA score=90.28).
A distinct plasma lipidomic signature and multi-omics network in depression of polycystic ovary syndrome.
Yan F, Sui M, Gao H … +2 more , Liu Y, Yu L
J Pharm Biomed Anal · 2026 Aug · PMID 41924769 · Publisher ↗
Patients with polycystic ovary syndrome (PCOS) are at an elevated risk of depression, yet the underlying mechanisms remain elusive. Emerging evidence implicates the gut-brain axis and systemic lipid homeostasis alteratio...
Patients with polycystic ovary syndrome (PCOS) are at an elevated risk of depression, yet the underlying mechanisms remain elusive. Emerging evidence implicates the gut-brain axis and systemic lipid homeostasis alterations as potential key contributors. We profiled untargeted plasma lipidomes of PCOS patients with and without comorbid depression (PCOS-DP) and integrated these data with our prior gut microbial and host transcriptomic datasets to construct multi-omics interaction networks. The causal role of the candidate gut microbial was preliminary explored in a germ-free PCOS mouse model using fecal microbiota transplantation, followed by behavioral phenotyping and ELISA-based protein quantification. We identified a distinct plasma lipidomic signature differentiating PCOS-DP from PCOS alone, characterized primarily by the downregulation of 26 lipid species. Most of these altered lipids were triacylglycerols (TAGs) enriched with FA18:1 and FA18:2, whose levels correlated with coagulation dysfunction. Multi-omics network analysis revealed significant interconnections between depression-associated gut microbiota (including Bacteroides eggerthii), specific altered lipids such as TAG (60:12/FA22:6), and host genes involved in inflammation (e.g., IL22, NLRP7), metabolism, and neural processes. Animal validation demonstrated that B. eggerthii colonization in PCOS mice specifically exacerbated anhedonia and hyperlocomotion, alongside modulating plasma IL-22 expression, suggesting its context-dependent neurobehavioral effect role. This study delineates a TAG-downregulated lipid signature with diagnostic potential and reveals a novel "gut microbiota-lipid-host gene" interaction network underpinning PCOS-DP, with B. eggerthii as a key microbial modulator of neurobehavioral phenotypes in the context of PCOS. These findings provide new pathophysiological insights and highlights potential diagnostic biomarkers for PCOS-DP.
NMR-based serum metabolomics reveals diabetes-linked metabolic reprogramming in early-stage chronic kidney disease.
Gupta U, Sahu A, Kaul A … +5 more , Mishra J, Yadav SC, Behera M, Baishya B, Sinha N
J Pharm Biomed Anal · 2026 Aug · PMID 41916254 · Publisher ↗
Early-stage chronic kidney disease (CKD) is usually asymptomatic, and the presence of type 2 diabetes mellitus (T2DM) accelerates metabolic alterations long before conventional clinical markers detect changes. Despite th...
Early-stage chronic kidney disease (CKD) is usually asymptomatic, and the presence of type 2 diabetes mellitus (T2DM) accelerates metabolic alterations long before conventional clinical markers detect changes. Despite their strong clinical association, the metabolic differences between early-stage non-diabetic CKD and diabetic CKD remain poorly understood, limiting early diagnosis and risk stratification. To identify disease-specific metabolic alterations and potential biomarkers, we employed quantitative proton NMR (¹H NMR) serum metabolomics (n = 100) in early-stage CKD (G1-G3B) patients, utilising untargeted polar metabolite profiling. Univariate and multivariate analyses (PCA, PLS-DA, Random Forest) clearly distinguished between diabetic CKD and non-diabetic CKD. Patients with diabetic CKD had lower levels of methionine, serine, and citrate, suggesting an early disturbance of energy and one-carbon metabolism. The ROC analysis (AUC = 0.77) showed a moderate level of diagnostic accuracy. Pathway enrichment analysis identified dysregulation of the tricarboxylic acid (TCA) cycle, pyruvate metabolism, glycine-serine-threonine metabolism, cysteine-methionine metabolism, and the one-carbon pool mediated by folate. Linear regression trend analyses across early-stage non-diabetic CKD, prediabetic CKD, and diabetic CKD revealed a gradual metabolic decline correlating with increasing glycemic burden. Collectively, these findings identify early metabolic signatures that elucidate the interplay between diabetic CKD and non- diabetic CKD, supporting improved patient stratification and targeted therapeutic strategies.
Simultaneous analysis of various anticancer drugs by supercritical fluid chromatography-mass spectrometry. Part II: Method validation and comparison with liquid chromatography.
Vallet V, Nguyen N, Rudaz S … +3 more , Bonnabry P, Guillarme D, Fleury-Souverain S
J Pharm Biomed Anal · 2026 Aug · PMID 41905099 · Publisher ↗
A complete SFC-MS/MS method validation enabling the simultaneous trace-level analysis of 27 conventional anticancer drugs (CADs) was performed. The selected drugs were the following: 5-fluorouracil, azacitidine, busulfan...
A complete SFC-MS/MS method validation enabling the simultaneous trace-level analysis of 27 conventional anticancer drugs (CADs) was performed. The selected drugs were the following: 5-fluorouracil, azacitidine, busulfan, carboplatin, cisplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, mitomycin, oxaliplatin, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine and vincristine. Accuracy profiles were obtained for all CADs. Trueness ranged between 71.0% and 119.8%, while repeatability (1.3-17.5%) and intermediate precision (2.0-24.9%) were determined for all compounds, with limits of quantification comprised between 0.1 and 25 ng.mL. These results were systematically compared with those obtained during the validation of a reference UHPLC-MS/MS method routinely used to analyze 25 of the 27 CADs contained in samples collected from work surfaces in a hospital pharmacy chemotherapy compounding unit. SFC-MS/MS method offered greater accuracy but was hampered by lower precision than the UHPLC-MS/MS method for most of the compounds. Furthermore, although the developed SFC-MS/MS method was characterized by a lower sensitivity, it allowed the quantification of compounds that were difficult to analyze by UHPLC-MS/MS, such as azacitidine and cisplatin, with analytical performance comparable to that obtained for the other CADs analyzed. This feature highlights the complementarity of the two chromatographic approaches in the context of CAD determination in a hospital environment.
First enantioselective determination of N-ethylpentedrone and its major phase-1 metabolites using supercritical fluid chromatography coupled with tandem mass spectrometry and its application to human oral fluid and urine samples.
Jorbenadze S, Tchelidze A, Sprega G … +10 more , Tkemaladze V, Dolidze G, Minutillo A, Farré M, Poyatos L, Papaseit E, Basile G, Farkas T, Busardo FP, Chankvetadze B
J Pharm Biomed Anal · 2026 Aug · PMID 41895187 · Publisher ↗
The enantioselective bioanalysis of synthetic cathinones and their metabolites remains analytically challenging. Due to the basic nature of these compounds, mobile phases with elevated pH are preferable for their analysi...
The enantioselective bioanalysis of synthetic cathinones and their metabolites remains analytically challenging. Due to the basic nature of these compounds, mobile phases with elevated pH are preferable for their analysis in high-performance liquid chromatography (HPLC). On the other hand, as it has been recently reported, cathinone derivatives are chemically and stereochemically instable, especially at high pH. As the alternative to HPLC, a supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) approach was developed in this study, to enable the chiral separation and detection of N-ethylpentedrone (NEP) and its major phase-1 metabolites. Careful selection of the chiral column and mobile phase compositions provided efficient retention and stereoselective resolution of both the parent compound and its polar metabolites. The applicability of the method was confirmed through the analysis of authentic human oral fluid (OF) and urine samples. The results of this study underscore the expanded analytical potential of SFC-MS/MS for chiral metabolite profiling and demonstrate its value as a complementary analytical tool to HPLC in forensic toxicology, particularly for new psychoactive substances.
Optimized UHPLC-derivatization method for low-level nitrite detection in pharmaceutical excipients.
Kormány R
J Pharm Biomed Anal · 2026 Aug · PMID 41895186 · Publisher ↗
This work presents a method optimization strategy for determining nitrite ions in pharmaceutical excipients. After derivatization, nitrite ions were analyzed using ultra-high-pressure liquid chromatography with UV detect...
This work presents a method optimization strategy for determining nitrite ions in pharmaceutical excipients. After derivatization, nitrite ions were analyzed using ultra-high-pressure liquid chromatography with UV detection. The article details how to achieve a sensitivity of 1 ng/mL (0.1 ppm) in pharmaceutical excipients while maintaining an analysis time of less than one minute. The results of nitrite measurements in several excipients obtained using the limit test to validate the analytical method are presented. The article also explains how to further reduce the detection limit while maintaining the analysis time. The advantage of the presented method is that it offers simple sample preparation and reproducible recovery above 90%. The article also shows what problems can be caused by incorrect sample preparation and excipient storage.
Microstructural analysis of PLGA-PEG-PLGA copolymer based on NMR spectroscopy using model compounds.
Strus B, Sitkowski J, Szterk A
J Pharm Biomed Anal · 2026 Aug · PMID 41886904 · Publisher ↗
This study presents a novel strategy for studying the microstructure of PLGA-PEG-PLGA triblock copolymers synthesized via the ROP mechanism using various organic catalysts. The use of model copolymers (PLG-PEG-PLG, PLA-P...
This study presents a novel strategy for studying the microstructure of PLGA-PEG-PLGA triblock copolymers synthesized via the ROP mechanism using various organic catalysts. The use of model copolymers (PLG-PEG-PLG, PLA-PEG-PLA) and multidimensional NMR spectroscopy (HSQC, HMBC, DOSY) enabled a more comprehensive characterization of the structure of PLGA-PEG-PLGA copolymers. The new method was verified by comparing the average molecular weights with the reference method-gel permeation chromatography. NMR analysis demonstrated a close correlation between the type of catalyst used, the monomer sequence arrangement, and the average molecular weights. The Zn(acac)₂ and Fe(acac)₃ catalysts demonstrated similar activity to the commonly used Sn(Oct)₂, making them potential substitutes in the synthesis of PLGA-PEG-PLGA copolymers. The proposed methodology provides detailed insight into copolymer microstructure, enabling more precise design of copolymers, which is essential for optimizing drug delivery systems.
A universal immunocapture LC-MS/MS method for humanized IgG1-based drugs in cynomolgus monkeys.
Pang P, Yin P, Tao Y … +5 more , Hong J, Xu J, Lin W, Qin Q, Gong L
J Pharm Biomed Anal · 2026 Aug · PMID 41886903 · Publisher ↗
The application of immunocapture LC-MS/MS in drug testing has expanded considerably over the past decade, offering significant advantages in analysis, development, and identification. In this study, we developed and vali...
The application of immunocapture LC-MS/MS in drug testing has expanded considerably over the past decade, offering significant advantages in analysis, development, and identification. In this study, we developed and validated a universal immunocapture LC-MS/MS assay for the detection of humanized IgG1-based drugs in cynomolgus monkey sera. The method selected a 12-amino acid characteristic peptide from the CH1 region of IgG1 as a quantification surrogate and used the heavy stable isotope-labeled same peptide as an internal standard. Furthermore, humanized IgG1-based drugs were immunocaptured using magnetic streptavidin beads pre-bound to biotinylated anti-human IgG1 Fc antibodies, followed by trypsin digestion. The related liquid chromatography was conducted on a Shiseido C18 column (2.0 mm × 100 mm, 3 μm) equipped on a Shimadzu Nexera X2 UHPLC system. Quantification of the humanized IgG1 -based drugs was performed on a LCMS-8050 triple quadrupole mass spectrometer using multiple reaction monitoring (MRM) mode with positive electrospray ionization. The developed assay was validated for parameters including calibration curve, precision, accuracy, selectivity, recovery, and stability. The obtained results all met the acceptance criteria valid for ligand-binding assays (LBAs). Besides, involving humanized IgG1 -based drugs exhibited good stability in cynomolgus monkey sera under different tested conditions. After validation, the assay was successfully applied to the pharmacokinetic studies of two humanized IgG1-based antibody-drug conjugates (ADCs), respectively, generating comparable pharmacokinetic profiles to related LBAs. Together, the results confirm the assay's reliability, universality, and feasibility for quantifying the target drugs.
Pharmacokinetic-pharmacodynamic modeling of Laportea bulbifera extract in adjuvant-induced arthritis rats via joint cavity microdialysis.
Chen S, Lu D, Yang K … +11 more , Huang Q, Liang Y, Xiao D, Zhang S, Jin Y, Li Y, Zheng L, Huang Y, Wang S, Xu H, Gong Z
J Pharm Biomed Anal · 2026 Aug · PMID 41886902 · Publisher ↗
This study developed a local pharmacokinetic-pharmacodynamic (PK-PD) model for Laportea bulbifera extract (LBE) in the joint cavity of adjuvant-induced arthritis (AA) rats using microdialysis technology. A stable intra-a...
This study developed a local pharmacokinetic-pharmacodynamic (PK-PD) model for Laportea bulbifera extract (LBE) in the joint cavity of adjuvant-induced arthritis (AA) rats using microdialysis technology. A stable intra-articular microdialysis sampling system was established, and the PK behavior of LBE in the joint cavities of normal and AA rats was compared using ultra performance liquid chromatography-tandem mass spectrometry analysis. The results demonstrated that the time to peak concentration and absorption half-life of the components were shortened in AA rats, whereas the area under the concentration-time curve increased. An increase in the apparent volume of distribution and a decrease in clearance were also observed, indicating accelerated absorption, increased exposure, and prolonged retention. An integrated PK-PD model was constructed by combining these data with pharmacodynamic data for tumor necrosis factor-alpha, interleukin-6, interleukin-1β, and rheumatoid factor (RF) obtained by enzyme-linked immunosorbent assay. Based on half maximal inhibitory concentration, the inhibitory potency of the five components against the four biomarkers was ranked as follows: kaempferol-3-O-rutinoside > neochlorogenic acid > rutin > chlorogenic acid > cryptochlorogenic acid. The effect compartment model revealed a linear relationship between RF and multiple components, underscoring RF's potential role as a key therapeutic target in the joint cavity. This study represents the first systematic elucidation of the local PK-PD characteristics of LBE, providing a scientific basis for developing this Miao medicinal herb and its clinical application in rheumatoid arthritis.
LC-MS/MS metabolite profiling, molecular networking and cyclooxygenase inhibition activity of Hornstedtia conoidea and Etlingera elatior extracts: In vitro and in silico insights.
Alcano JC, Laserna AKC, Quimque MTJ … +3 more , Pelobello DHD, Camacho DH, Barbosa GB
J Pharm Biomed Anal · 2026 Aug · PMID 41880928 · Publisher ↗
Inflammation is a complex physiological response implicated in infectious and metabolic diseases. Although nonsteroidal anti-inflammatory drugs (NSAIDs) effectively reduce inflammation through cyclooxygenase (COX) inhibi...
Inflammation is a complex physiological response implicated in infectious and metabolic diseases. Although nonsteroidal anti-inflammatory drugs (NSAIDs) effectively reduce inflammation through cyclooxygenase (COX) inhibition, their poor isoform selectivity often leads to gastrointestinal and renal side effects. To explore natural alternatives, the anti-inflammatory activity and untargeted metabolite profiles of two Zingiberaceae species, Etlingera elatior (EE) inflorescence and the Philippine endemic Hornstedtia conoidea (HC) infructescence, were investigated. LC-MS/MS-based metabolite profiling combined with molecular networking revealed a diverse array of polyphenolic phytochemicals in both plants. Crude methanol-water extracts of EE and HC inhibited COX activity in vitro, with EE exhibiting stronger inhibition. Molecular docking demonstrated moderate to strong binding affinities of polyphenols toward both COX isoforms, with oligomeric procyanidins favoring COX-1 and flavonoid glycosides preferentially accommodated in COX-2. Molecular dynamics simulations of top-ranked complexes confirmed stable ligand binding, preserved structural integrity, and isoform-specific stabilization patterns. Comparative metabolomic analysis indicated that differences between EE and HC were primarily driven by phenolic compounds, with cyanidin glycosides as differentially abundant metabolites with theoretical binding preference to COX-2 isoform over COX-1. Overall, this integrative strategy combining metabolomics, bioassays, and computational modeling provides molecular-level insights supporting EE and HC as promising sources of natural COX inhibitors.
Unraveling the phenolic profiles of Clinopodium bolivianum (Benth.) Kuntze and Minthostachys mollis (Benth.) Griseb.: A comprehensive LC-QtoF metabolomic study of underexplored Peruvian medicinal plants.
García-Acosta N, Moratilla-Rivera I, Jordán M … +4 more , Balderas C, Clavo ZM, Rodríguez JL, Mateos R
J Pharm Biomed Anal · 2026 Aug · PMID 41880927 · Publisher ↗
Medicinal plants remain a primary healthcare resource worldwide, particularly in regions with strong cultural traditions and limited economic development. In Peru, muña [Minthostachys mollis (Benth.) Griseb.] and inca mu...
Medicinal plants remain a primary healthcare resource worldwide, particularly in regions with strong cultural traditions and limited economic development. In Peru, muña [Minthostachys mollis (Benth.) Griseb.] and inca muña [Clinopodium bolivianum (Benth.) Kuntze], both Lamiaceae species used for gastrointestinal and anti-inflammatory purposes, are poorly characterized at the metabolomic level, limiting the availability of phytochemical data required to ensure the quality and authenticity of commercial preparations. This study aimed to unravel and comprehensively characterize the phenolic metabolomes of both species and evaluate their antioxidant capacity, providing novel chemical evidence for species differentiation assessment. The samples underwent a two-stage solid-liquid extraction, and the resulting extracts were analyzed using Folin-Ciocalteu, FRAP and ABTS assays, and extensively profiled by LC-ESI-QToF based metabolomics. Morphological characterization was performed by light microscopy. The results showed that inca muña had a higher phenolic content, expressed as milligrams of gallic acid equivalents (mg GAE) per 200 mL of infusion (201 vs. 134 mg GAE/200 mL, and superior antioxidant capacity in FRAP and ABTS assays. A total of fifty-one phenolic compounds were tentatively identified, predominantly flavonols, flavones, hydroxybenzoic acids, and hydroxycinnamic acids. Multivariate metabolomic analysis revealed distinct phenolic profiles between species, highlighting clear interspecific differences. Muña stood out for phenylacetaldehyde, galloyl sucrose, and isoflavones, while inca muña showed higher levels of cudraflavone and naringenin, proposed as potential discriminant biomarkers. Together, these findings unravel the phenolic metabolomes of two underexplored Peruvian medicinal plants, support their antioxidant potential, and provide a comprehensive metabolomic basis for chemical differentiation and paved the way to a more accurate authenticity assessment in commercial herbal preparations.
Study of GJKBW against RA based on the Chinmedomics combined LIP-MS molecular fishing technology: A new strategy for discovering the therapeutic material basis.
Zha X, Yao LY, Gong WW … +9 more , Li XY, Zhang L, Chen Y, Xia Q, Ruan JH, Tan R, Tao L, Shen XC, Liu SB
J Pharm Biomed Anal · 2026 Aug · PMID 41875839 · Publisher ↗
Rheumatoid arthritis (RA) is a major chronic autoimmune disease. Current conventional drugs face significant challenges, including severe side effects, high recurrence rates, and unsuitability for long-term use. In contr...
Rheumatoid arthritis (RA) is a major chronic autoimmune disease. Current conventional drugs face significant challenges, including severe side effects, high recurrence rates, and unsuitability for long-term use. In contrast, traditional Chinese medicine (TCM) has garnered increasing attention due to its multi-target regulatory advantages. Guan Jie Ke Be Wan (GJKBW) demonstrates notable therapeutic efficacy, but its therapeutic material basis and mechanisms of action remain unclear, which limits its precise clinical application and therapeutic optimization. Based on this, this study adopted Chinmedomics combined with Limited Proteolysis-coupled Mass Spectrometry (LIP-MS) molecular fishing technology to screen the key metabolic pathways in RA and analyze the relevant protein targets in these pathways. Key protein targets were extracted to identify the potential therapeutic material basis of GJKBW. LIP-MS and molecular dynamics analysis were employed to validate the reliability of its specific binding to the target proteins, and finalized the results and related mechanisms. Finally, the linoleic acid metabolic pathway was identified as a key pathway in RA. It was discovered that GJKBW exerted its therapeutic effects by targeting key proteins such as FADS2, PLA2G4A, and PLA2G15 to regulate linoleic acid metabolism. This regulation subsequently influenced the downstream metabolism of arachidonic acid, ultimately leading to the inhibition of the expression of related inflammatory factors. Isobergapten and Wogonin are identified as the therapeutic material basis for GJKBW within this mechanism of action. This study provides a novel paradigm for the "quantity-effect" correlation research of TCM formulas, incorporating "bioinformatics prediction-multi-omics validation-LIP-MS screening-molecular dynamics analysis".
A progressive screening strategy by combining UHPLCQTOF-MS and machine learning for distinguishing different varieties of Citri Reticulatae Pericarpium.
Hu D, Zhong M, Pei Z … +9 more , Zheng L, Luo J, Jiang Q, Chen Y, Cao Q, Lin L, Zou W, Deng W, Li H
J Pharm Biomed Anal · 2026 Aug · PMID 41875838 · Publisher ↗
This study employed UHPLC-QTOF-MS-based untargeted metabolomics, integrated with chemometrics and machine learning, to discriminate between varieties of Citri Reticulatae Pericarpium (CRP). To identify specific markers b...
This study employed UHPLC-QTOF-MS-based untargeted metabolomics, integrated with chemometrics and machine learning, to discriminate between varieties of Citri Reticulatae Pericarpium (CRP). To identify specific markers between each pair of varieties more precisely, a progressive screening strategy was adopted. Initially, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) screened 46 universal differential metabolites across the four varieties. Subsequently, pairwise orthogonal partial least squares discriminant analysis (OPLS-DA) applied to these universal metabolites facilitated the detection of specific differential metabolites. LC-MS analysis identified a total of 268 metabolites. PCA revealed significant metabolic differences among the four CRP varieties, while PLS-DA screened 46 universal differential metabolites (VIP > 1). 9 machine learning discrimination models constructed from these 46 metabolites exhibited excellent performance (with accuracy, etc. > 0.9461) and successfully discriminated externally validated CRP samples from different varieties with a 100% recognition rate. Further, pairwise OPLS-DA based on the universal differential metabolites screened out 10 universal specific differential metabolites (VIP > 1), including 5-O-demethylnobiletin. Notably, nobiletin distinguished pharmacopoeia from non-pharmacopoeia CRP varieties. Finally, integrative analyses linked these findings to their biological significance, attributing differential flavonoid accumulation among CRP varieties to molecular evolutionary mechanisms driven by genetic background-dependent methylation and glycosylation processes. This study demonstrates the considerable potential of UHPLCQTOF-MS-based untargeted metabolomics for distinguishing CRP varieties, providing a useful reference for market quality control and clinical practice.
Identification of ursolic acid from Wumei as a syk-targeting anti-allergic agent using a piezoresistive cantilever biosensor.
Xu Z, Miao B, Gu Z … +3 more , Hu Y, Tang D, Li J
J Pharm Biomed Anal · 2026 Aug · PMID 41865691 · Publisher ↗
Wumei (WM), a historical food and medicine homology fruit in China, is reported to have anti-allergic effect, yet its active components and mechanisms remain unclear. Here, a novel spleen tyrosine kinase-based piezoresis...
Wumei (WM), a historical food and medicine homology fruit in China, is reported to have anti-allergic effect, yet its active components and mechanisms remain unclear. Here, a novel spleen tyrosine kinase-based piezoresistive cantilever array (Syk-PCA) biosensor was developed for screening anti-allergic components in WM. Once the biosensor composition was confirmed by X-ray photoelectron spectroscopy (XPS), its specificity was evaluated based on the differential electrochemical responses toward piceatannol and protocatechualdehyde. The biosensors were subsequently used to screen for Syk-binding compound of WM extract as a predictor of potential anti-allergic properties, including succinic acid, tartaric acid, chlorogenic acid, citric acid, and ursolic acid. The biosensor demonstrated high specificity and sensitivity, achieving a femtomolar-level interaction for ursolic acid with a surface equilibrium dissociation constant (K) of 2.37 fM and a linear detection range from 1 fM to 1 pM. Using this platform, ursolic acid was identified as the key active component targeting Syk. The activity was validated through in vitro and in silico approaches, including RBL-2H3 cell model, cellular thermal shift assay (CETSA), molecular docking and molecular dynamics simulation. The binding affinity between ursolic acid and Syk was demonstrated by the elevated thermostability of ursolic acid-Syk complex. Molecular docking and molecular dynamics simulation results indicated that the complex remained stable, with interactions mediated by hydrogen bonds and hydrophobic interactions. These findings reveal that ursolic acid exerts anti-allergic effects by targeting Syk, and the Syk-PCA biosensor provides a rapid, cost-effective tool for targeted drug discovery.
Matrix-dependent degradation kinetics and impurity fingerprinting of cannabidiol (CBD) in polymeric and lipid preservation systems.
Haidery QUA, Han B, Saeed R … +3 more , Yan C, Ma X, Zheng W
J Pharm Biomed Anal · 2026 Aug · PMID 41864105 · Publisher ↗
Cannabidiol (CBD), a non-psychoactive terpenophenolic compound derived from Cannabis sativa, exhibits broad-spectrum pharmacological activities but is highly susceptible to oxidative, photolytic, and thermal degradation,...
Cannabidiol (CBD), a non-psychoactive terpenophenolic compound derived from Cannabis sativa, exhibits broad-spectrum pharmacological activities but is highly susceptible to oxidative, photolytic, and thermal degradation, making it challenging to preserve and use in therapeutics. Therefore, this study compares the preservation efficiency of a powder-based hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion-complex system for cannabinoid stability and solubility and medium-chain triglyceride (MCT) oil, a common lipid-based carrier in commercial formulations. Formulation characterizations, including CBD content (HPLC), color change, solvent residues, moisture, particle size, and zeta potential, were measured. DPPH experiments revealed that the HP-β-CD complex exhibited higher antioxidant activity (89.2%, EC₅₀ = 45.3 µg/mL) than the MCT oil system (83.6%, EC₅₀ = 58.7 µg/mL), with ascorbic acid serving as the control (EC₅₀ = 12.4 µg/mL). Additionally, photostability testing (8000 lux) demonstrated superior CBD retention in the HP-β-CD complex (>90%) compared with MCT oil (∼20%), indicating substantial light-induced degradation in the oil system. HP-β-CD complex retained 92-93% CBD (k = 0.0084 week⁻¹; t₁/₂ = 82.5 weeks) versus 88% in MCT oil. At 40 °C, HP-β-CD complex preserved 86-87% CBD. GC-FID/GC-MS showed that HP-β-CD powder preserved CBD with only trace degradation (<0.1-1.0%). In contrast, MCT oil produced higher cannabinoid by-products (0.1-6.21%), and greater antioxidant degradation (2.5-8.6% vs 0.5-2.1%). The results suggested that CBD degradation follows matrix-dependent kinetics, with cyclodextrin encapsulation significantly reducing the apparent degradation rate constants relative to oil-based solubilization under identical stress conditions.
Simultaneous quantification of active ingredients after the combination of Shenqi Fuzheng injection and docetaxel in vitro and in rabbits.
Luo Y, Zeng D, Liu J … +7 more , Wang J, Zhao M, Hong Z, Mabood KF, Jamil A, Li W, Hong B
J Pharm Biomed Anal · 2026 Aug · PMID 41864104 · Publisher ↗
Shenqi Fuzheng injection (SFI), known for its ability to replenish Qi and strengthen vital energy, is frequently combined with docetaxel, a first-line chemotherapeutic agent, for the treatment of breast cancer in clinica...
Shenqi Fuzheng injection (SFI), known for its ability to replenish Qi and strengthen vital energy, is frequently combined with docetaxel, a first-line chemotherapeutic agent, for the treatment of breast cancer in clinical practice. Although the combined regimen (SFI-docetaxel) demonstrated proven efficacy against breast cancer, no reports have addressed the alterations in the active concentrations of components in or pharmacokinetic behavior of SFI-docetaxel. Thus, a ultra performance liquid chromatography (UPLC) method was used to investigate alterations in the active components of SFI-docetaxel, and liquid chromatography-tandem mass spectrometry (LCMS/MS) analysis was used to characterize the pharmacokinetic behavior of both the active components of SFI and docetaxel in rabbits. After combination treatment with docetaxel, the concentrations of lobetyolin significantly decreased, whereas the concentrations of quercetin, formononetin, and astragaloside IV significantly increased (p < 0.05). Pharmacokinetics revealed that docetaxel had the longest half-life (T) of 12.159 h, followed by that of astragaloside IV (T = 10.139 h), whereas all the other active components had T values less than 9 h. All the components reached the peak concentration time (T) at 0.033 h, which is consistent with intravenous administration characteristics, indicating immediate drug action without an absorption phase. This work not only elucidated changes in the concentrations of active components in SFI-docetaxel but also revealed the pharmacokinetic characteristics of both the effective components and docetaxel, thereby providing significant implications for advancing integrated Chinese-Western medicine in cancer treatment and facilitating clinical applications of traditional Chinese medicine formulae.
Self-assembled precipitates from Gegen Qinlian decoction: Physicochemical characterization, in vivo and in vitro behaviors.
Chen Z, Luo Z, Xia T … +1 more , Tan X
J Pharm Biomed Anal · 2026 Aug · PMID 41864103 · Publisher ↗
Gegen Qinlian decoction (GQD), a traditional Chinese medicine used to treat infectious diarrhea, forms self-precipitates (GQD-P) during decoction. Although GQD-P and the supernatant (GQD-S) share an identical chemical co...
Gegen Qinlian decoction (GQD), a traditional Chinese medicine used to treat infectious diarrhea, forms self-precipitates (GQD-P) during decoction. Although GQD-P and the supernatant (GQD-S) share an identical chemical composition, their physicochemical properties and in vivo behavior are not yet fully understood. This study aimed to investigate the physicochemical, in vitro, and in vivo properties of GQD-P, and to elucidate its unique role in the decoction's holistic efficacy. The morphology and pH-dependent dissolution of GQD-P were analyzed. Components in GQD, GQD-S, and GQD-P were quantified using HPLC, while pharmacokinetics of nine components were compared in rats administered GQD, GQD-S, or GQD-P using UPLC-MS/MS. GQD-P consisted of nanospheres whose dissolution was markedly enhanced under acidic, but not enzymatic, conditions. Baicalin and berberine were the main components of the primary precipitate framework. GQD-P components showed significantly prolonged MRT and T, and delayed T compared to GQD-S. The whole decoction exhibited a biphasic profile combining features of both phases, with GQD-P acting as a pH-triggered, sustained-release reservoir. Together with the rapid-release supernatant, it creates a biphasic system prolonging systemic exposure and collectively underpins the comprehensive efficacy of GQD.
Identification of Novel Anti- non-small cell lung cancer (NSCLC) Peptide in toad Skin（Chan Pi） Extract through Integrated Peptidomics and in silico Screening.
Tu X, Wu J, Dong Y … +6 more , Liang R, Zhan M, Yan J, Wang J, Huang X, Zhang P
J Pharm Biomed Anal · 2026 Aug · PMID 41856053 · Publisher ↗
Toad skin (Bufo bufo gargarizans Cantor), known as Chan Pi in traditional Chinese medicine, has long been recognized for its therapeutic potential, particularly in cancer treatment. While the pharmacological activities o...
Toad skin (Bufo bufo gargarizans Cantor), known as Chan Pi in traditional Chinese medicine, has long been recognized for its therapeutic potential, particularly in cancer treatment. While the pharmacological activities of small molecules in toad skin such as bufadienolides have been extensively studied, peptides-another class of bioactive molecules-remain largely unexplored. In this study, we employed a peptidomics-based approach combined with in silico screening and experimental validation to identify novel bioactive peptides with potential anticancer properties from toad skin extracts. Approximately 2500 distinct peptides were identified using both database searching and de novo sequencing. Computational screening with two predictive models identified 26 candidate peptides with bioactivity scores exceeding 0.75. Among them, three peptides with potential anti-lung cancer activity were synthesized for in vitro evaluation against NSCLC cell lines, A549 and H1975. Peptide STPECLLGMWK exerts selective anti-proliferative effects on TKI resistant H1975 lung cancer cells in a dose-dependent manner. These findings provide new insights into the peptide composition of toad skin extracts and highlight their potential as a source of novel anticancer agents, laying the groundwork for future cancer therapeutics development.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe